Microgliosis: a double-edged sword in the control of food intake

Maintaining energy balance is essential for survival and health. This physiological function is controlled by the brain, which adapts food intake to energy needs. Indeed, the brain constantly receives a multitude of biological signals that are derived from digested foods or that originate from the gastrointestinal tract, energy stores (liver and adipose tissues) and other metabolically active organs (muscles). These signals, which include circulating nutrients, hormones and neuronal inputs from the periphery, collectively provide information on the overall energy status of the body. In the brain, several neuronal populations can specifically detect these signals. Nutrient-sensing neurons are found in discrete brain areas and are highly enriched in the hypothalamus. In turn, specialized brain circuits coordinate homeostatic responses acting mainly on appetite, peripheral metabolism, activity and arousal. Accumulating evidence shows that hypothalamic microglial cells located at the vicinity of these circuits can influence the brain control of energy balance. However, microglial cells could have opposite effects on energy balance, that is homeostatic or detrimental, and the conditions for this shift are not totally understood yet. One hypothesis relies on the extent of microglial activation, and nutritional lipids can considerably change it

Mitochondrial Dynamin-Related Protein 1 (DRP1) translocation in response to cerebral glucose is impaired in a rat model of early alteration in hypothalamic glucose sensing

OBJECTIVE: Hypothalamic glucose sensing (HGS) initiates insulin secretion (IS) via a vagal control, participating in energy homeostasis. This requires mitochondrial reactive oxygen species (mROS) signaling, dependent on mitochondrial fission, as shown by invalidation of the hypothalamic DRP1 protein. Here, our objectives were to determine whether a model with a HGS defect induced by a short, high fat-high sucrose (HFHS) diet in rats affected the fission machinery and mROS signaling within the mediobasal hypothalamus (MBH). METHODS: Rats fed a HFHS diet for 3 weeks were compared with animals fed a normal chow. Both in vitro (calcium imaging) and in vivo (vagal nerve activity recordings) experiments to measure the electrical activity of isolated MBH gluco-sensitive neurons in response to increased glucose level were performed. In parallel, insulin secretion to a direct glucose stimulus in isolated islets vs. insulin secretion resulting from brain glucose stimulation was evaluated. Intra-carotid glucose load-induced hypothalamic DRP1 translocation to mitochondria and mROS (H2O2) production were assessed in both groups. Finally, compound C was intracerebroventricularly injected to block the proposed AMPK-inhibited DRP1 translocation in the MBH to reverse the phenotype of HFHS fed animals. RESULTS: Rats fed a HFHS diet displayed a decreased HGS-induced IS. Responses of MBH neurons to glucose exhibited an alteration of their electrical activity, whereas glucose-induced insulin secretion in isolated islets was not affected. These MBH defects correlated with a decreased ROS signaling and glucose-induced translocation of the fission protein DRP1, as the vagal activity was altered. AMPK-induced inhibition of DRP1 translocation increased in this model, but its reversal through the injection of the compound C, an AMPK inhibitor, failed to restore HGS-induced IS. CONCLUSIONS: A hypothalamic alteration of DRP1-induced fission and mROS signaling in response to glucose was observed in HGS-induced IS of rats exposed to a 3 week HFHS diet. Early hypothalamic modifications of the neuronal activity could participate in a primary defect of the control of IS and ultimately, the development of diabetes.Rôle des connexines astrocytaires dans le mécanisme de détection hypothalamique du glucose : implication sur le contrôle nerveux du métabolisme énergétiqu

Postprandial hyperglycemia stimulates neuroglial plasticity in hypothalamic POMC neurons after a balanced meal

Mechanistic studies in rodents evidenced synaptic remodeling in neuronal circuits that control food intake. However, the physiological relevance of this process is not well defined. Here, we show that the firing activity of anorexigenic POMC neurons located in the hypothalamus is increased after a standard meal. Postprandial hyperactivity of POMC neurons relies on synaptic plasticity that engages pre-synaptic mechanisms, which does not involve structural remodeling of synapses but retraction of glial coverage. These functional and morphological neuroglial changes are triggered by postprandial hyperglycemia. Chemogenetically induced glial retraction on POMC neurons is sufficient to increase POMC activity and modify meal patterns. These findings indicate that synaptic plasticity within the melanocortin system happens at the timescale of meals and likely contributes to short-term control of food intake. Interestingly, these effects are lost with a high-fat meal, suggesting that neuroglial plasticity of POMC neurons is involved in the satietogenic properties of foods.Contrôle nerveux de la prise alimentaire et du métabolisme par une molécule neurale d'adhésion cellulaireISITE " BFCRéseau d'Innovation sur les Voies de Signalisation en Sciences de la Vi

Les productions céramiques médiévales et modernes de Dijon : un état de la question à partir des données issues des fouilles du Tramway

National audienc

Sécurité et transmission haut débit dans les véhicules : apport des courants porteurs

National audienc

Les céramiques de raffinage dans les ports atlantiques : interactions économiques en métropole et avec les Antilles entre le XVIe et le XIXe s.

Programme collectif de recherche 2014-2016, rapport 201

" Vestiges d'un habitat rural du XIe siècle : le Nouzeau à Gurgy (Yonne) "

Jolly V., Ravoire F. (dir.)International audienceLe site du Nouzeau à Gurgy (Yonne) est un habitat du Moyen Âge central, caractérisé par des structures fossoyées (cabanes excavées, fosses, silos) qui paraît assez isolé – mais la limite sud de son extension n’a pu être fouillée. Son statut a pu être appréhendé grâce à la découverte d’un outillage métallique abondant, varié et caractéristique. Un assemblage de restes fauniques témoigne des pratiques agro-pastorales spécifiques qui pourraient révéler un site d’élevage d’ovins, bien que des volailles, des porcs, des bovins et des équidés soient aussi présents. Des couteaux, une pointe de flèche et surtout des éléments de serrures, une coupelle et une clé de porte sont autant de témoins matériels singuliers dans un tel contexte. Le mobilier céramique, abondant, permet de dater le site et d’entrevoir ses réseaux d’approvisionnement en poterie de terre. Cette exploitation pourrait être liée à une dépendance monastique de l’abbaye Saint-Germain d’Auxerre

" Vestiges d'un habitat rural du XIe siècle : le Nouzeau à Gurgy (Yonne) "

Jolly V., Ravoire F. (dir.)International audienc

" Vestiges d'un habitat rural du XIe siècle : le Nouzeau à Gurgy (Yonne) "

Jolly V., Ravoire F. (dir.)International audienc

The gliotransmitter ACBP controls feeding and energy homeostasis via the melanocortin system

Glial cells have emerged as key players in the central control of energy balance and etiology of obesity. Astrocytes play a central role in neural communication via the release of gliotransmitters. Acyl-CoA binding protein (ACBP)-derived endozepines are secreted peptides that modulate the GABAA receptor. In the hypothalamus, ACBP is enriched in arcuate nucleus (ARC) astrocytes, ependymocytes and tanycytes. Central administration of the endozepine octadecaneuropeptide (ODN) reduces feeding and improves glucose tolerance, yet the contribution of endogenous ACBP in energy homeostasis is unknown. We demonstrated that ACBP deletion in GFAP+ astrocytes, but not in Nkx2.1-lineage neural cells, promoted diet-induced hyperphagia and obesity in both male and female mice, an effect prevented by viral rescue of ACBP in ARC astrocytes. ACBP-astrocytes were observed in apposition with proopiomelanocortin (POMC) neurons and ODN selectively activated POMC neurons through the ODN-GPCR but not GABAA, and supressed feeding while increasing carbohydrate utilization via the melanocortin system. Similarly, ACBP overexpression in ARC astrocytes reduced feeding and weight gain. Finally, the ODN-GPCR agonist decreased feeding and promoted weight loss in ob/ob mice. These findings uncover ACBP as an ARC gliopeptide playing a key role in energy balance control and exerting strong anorectic effects via the central melanocortin system.Dissection des mécanismes hypothalamiques impliqués dans la détection du statut nutritionnel et régulation de la prise alimentaire via les interactions entre mTORC1, les mélanocortines et les endocannabinoïdes.Rôle du récepteur aux cannabinoïdes de type 1 mitochondriale dans les circuits hypothalamiques et son interaction avec la voie mTORC1 dans l'obésité